含三氮唑杂环化合物的合成及生物活性研究
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摘要
根据以DNA为靶点抗肿瘤药物的作用机理,通过对平面性良好的1,8-萘酰亚胺和苊醌类化合物进行结构改造,本文设计、合成、表征了三系列以DNA为靶点的抗肿瘤化合物:
以Click Chemistry方法,设计、合成了一系列新型含1,2,3-三唑基的萘酰亚胺类衍生物,并对其光谱性质、DNA嵌入能力、DNA光敏切割活性和抗肿瘤活性进行了研究。荧光光谱法、粘度测定、圆二色谱法研究化合物与CT DNA相互作用的结果表明该化合物具有一定的DNA嵌入性能,嵌入常数为10~4～10~5M~(-1),可作为有效的DNA靶向分子;DNA光敏切割活性试验结果表明:该系列化合物具有较强的光敏损伤活性;抗肿瘤活性研究结果表明该系列化合物具有明显的体外抑制肿瘤细胞生长活性,特别是带有硫吗啉基取代的化合物N2对7721肝癌细胞有很高的抑制活性,IC_(50)值达到0.478μM。
以Click Chemistry方法,设计、合成了一系列新型含1,2,3-三唑基苊并杂环类化合物,对其光谱性质、DNA结合能力、DNA光敏切割活性和抗肿瘤活性进行了研究。紫外光谱法、粘度测定、圆二色谱法研究化合物与CT DNA的作用模式为部分嵌入,并伴随一定的静电堆积;DNA光敏切割试验表明:该系列化合物具有较强的光敏损伤活性。其中带有两个氰基的化合物E2表现出最好的DNA光敏切割活性,与它高效的细胞抑制性能相一致。
以Click Chemistry方法,设计、合成了两个新型含1,2,3-三唑基萘酰亚胺类荧光团。光谱测定和细胞标记试验表明该类化合物可以应用于活细胞的生物影像,具有开发为荧光探针的应用前景,为今后在其基础上修饰进行荧光标记做了有益的探索。
Based on the mechanism of antitumor agents that target DNA,three series of compounds were designed,synthesized and charactered by modifying the structures of the naphthalimide skeleton and acenaphthenequinone derivatives,which consist of flat and rigid structures..
A series of 1,2,3-triazol-1,8-naphthalimide derivatives were designed and synthesized via "Click Chemistry".Their spectra properties,DNA intercalative,DNA photo-damaging and antitumor activities were evaluated.The scatchard binding constants between CT DNA with N1-N6 were monitored by fluorescence spectroscopy technique.The result showed that they could effectively intercalate into the CT DNA and the scatchard binding constants reached 10~4-10~5 M~(-1),So they could be used as effective DNA-target molecules.The antitumor activities test of these compounds exhibited efficient activities against 7721 and BGC-823 cell lines,especially compound N2 with thiomorpholinyl substituent,the IC_(50) value against 7721 cell was 0.478×10~(-6) M.
A series of Novel 1,2,3-triazol-acenaphtho-fused heterocyclic compounds were designed and synthesized via "Click Chemistry".Their spectra properties,DNA intercalative,DNA photo-damaging and antitumor activities were evaluated.DNA-binding abilities of the E1-E6 were investigated by UV-vis,CD spectroscopic techniques and viscosity measurement,The results indicated that the compounds binded to DNA partly via intercalation,accompanied by kind of aggregation.DNA photo-damaging assayes showed that these compounds could effectively cleave supercoiled DNA,especially compound E2 with two cyanogen groups, which was in accordance with its excellent antitumor activity.
Two novel 1,2,3-triazol-1,8-naphthalimide fluorophores were designed and synthesized via "Click Chemistry".Cell uptake experiments with fluorescence images indicated that V1 and V2 could be used for bioimaging in living cells,which implied the potentials of the fluorescence dyes V1 and V2 used as fluorescence agents.
以Click Chemistry方法,设计、合成了一系列新型含1,2,3-三唑基的萘酰亚胺类衍生物,并对其光谱性质、DNA嵌入能力、DNA光敏切割活性和抗肿瘤活性进行了研究。荧光光谱法、粘度测定、圆二色谱法研究化合物与CT DNA相互作用的结果表明该化合物具有一定的DNA嵌入性能,嵌入常数为10~4～10~5M~(-1),可作为有效的DNA靶向分子;DNA光敏切割活性试验结果表明:该系列化合物具有较强的光敏损伤活性;抗肿瘤活性研究结果表明该系列化合物具有明显的体外抑制肿瘤细胞生长活性,特别是带有硫吗啉基取代的化合物N2对7721肝癌细胞有很高的抑制活性,IC_(50)值达到0.478μM。
以Click Chemistry方法,设计、合成了一系列新型含1,2,3-三唑基苊并杂环类化合物,对其光谱性质、DNA结合能力、DNA光敏切割活性和抗肿瘤活性进行了研究。紫外光谱法、粘度测定、圆二色谱法研究化合物与CT DNA的作用模式为部分嵌入,并伴随一定的静电堆积;DNA光敏切割试验表明:该系列化合物具有较强的光敏损伤活性。其中带有两个氰基的化合物E2表现出最好的DNA光敏切割活性,与它高效的细胞抑制性能相一致。
以Click Chemistry方法,设计、合成了两个新型含1,2,3-三唑基萘酰亚胺类荧光团。光谱测定和细胞标记试验表明该类化合物可以应用于活细胞的生物影像,具有开发为荧光探针的应用前景,为今后在其基础上修饰进行荧光标记做了有益的探索。
Based on the mechanism of antitumor agents that target DNA,three series of compounds were designed,synthesized and charactered by modifying the structures of the naphthalimide skeleton and acenaphthenequinone derivatives,which consist of flat and rigid structures..
A series of 1,2,3-triazol-1,8-naphthalimide derivatives were designed and synthesized via "Click Chemistry".Their spectra properties,DNA intercalative,DNA photo-damaging and antitumor activities were evaluated.The scatchard binding constants between CT DNA with N1-N6 were monitored by fluorescence spectroscopy technique.The result showed that they could effectively intercalate into the CT DNA and the scatchard binding constants reached 10~4-10~5 M~(-1),So they could be used as effective DNA-target molecules.The antitumor activities test of these compounds exhibited efficient activities against 7721 and BGC-823 cell lines,especially compound N2 with thiomorpholinyl substituent,the IC_(50) value against 7721 cell was 0.478×10~(-6) M.
A series of Novel 1,2,3-triazol-acenaphtho-fused heterocyclic compounds were designed and synthesized via "Click Chemistry".Their spectra properties,DNA intercalative,DNA photo-damaging and antitumor activities were evaluated.DNA-binding abilities of the E1-E6 were investigated by UV-vis,CD spectroscopic techniques and viscosity measurement,The results indicated that the compounds binded to DNA partly via intercalation,accompanied by kind of aggregation.DNA photo-damaging assayes showed that these compounds could effectively cleave supercoiled DNA,especially compound E2 with two cyanogen groups, which was in accordance with its excellent antitumor activity.
Two novel 1,2,3-triazol-1,8-naphthalimide fluorophores were designed and synthesized via "Click Chemistry".Cell uptake experiments with fluorescence images indicated that V1 and V2 could be used for bioimaging in living cells,which implied the potentials of the fluorescence dyes V1 and V2 used as fluorescence agents.
引文
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